A fundamental aspect of our existence is the fact that we move through space. We do not do so randomly; rather, we use a variety of different strategies to reach our navigational goals efficiently. One such strategy is landmark-based navigation (LBN), which is the use of stable landmarks to determine one's location and orientation relative to the enduring spatial structure of the world. The current application describes a competing renewal of a research program in which we use functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and cognitive behavioral testing to understand the neural systems that underlie LBN. Under the theoretical scheme we have developed, LBN involves three cognitive mechanisms: a landmark recognition mechanism, a localization/orientation mechanism, and a route planning mechanism. During the initial funding period, we used multivoxel pattern analysis (MVPA) of fMRI data to demonstrate that the parahippocampal place area (PPA) supports landmark recognition and the retrosplenial complex (RSC) supports localization/orientation. These results indicate that the neural network involved in LBN can be fractionated into functional subsystems tied to the three cognitive mechanisms. Our goals in the next funding period are to use these discoveries as a springboard to understand the mechanistic operation of the LBN system and to extend the investigation to encompass route planning. Aim 1 is to delineate the information processing functions of the landmark recognition mechanism in the PPA and to identify its functional inputs. Aim 2 is to understand the how the RSC uses external features and egocentric experience to mediate localization/orientation. Aim 3 is to identify and characterize the neural mechanisms that support route planning in RSC and the medial temporal lobe (MTL). If successful, this research will result in a detailed theory of the neural basis of landmark-based navigation. This knowledge will have important health implications in two domains. First, understanding the mechanisms that underlie LBN is critical for the development of rehabilitation strategies and navigational aids for the blind. Second, because the brain regions investigated are often impacted early in neurodegenerative diseases such as Alzheimer's dementia, the knowledge gained about these systems will be useful for diagnosing and managing these diseases.